The population genetics of mutations: good, bad and indifferent

At its heart evolution@home investigates how DNA changes affect populations in the long run. The scene for this work has been set by the research of evolutionary biologists like Brian Charlesworth. To mark his 65th birthday on 29 April 2010 and his many significant contributions, a themed issue of Philosophical Transactions of the Royal Society B has been published on 'The population genetics of mutations: good, bad and indifferent'. It comprises articles by a number of influential individuals who have been associated with Brian over the years.

The fruitfly Drosophila has many advantages as a study system for investigating population genetics questions, which is why Brian Charlesworth has focussed much of his research on understanding evolutionary questions in Drosophila.

All genetic variation comes initially from
mutations in the DNA, such as produced by miscopying of the parental genome.
Hence mutation provides the fuel for evolution. Whilst mutations occur in
individuals and affect individuals, to study their fate we need to consider the
whole population in which they occur. An individual mutation is either lost
from the population with a certain probability, or it is eventually fixed in
the population by replacing all DNA without this mutation. The great majority
of mutations are harmful (the 'bad') and selection is expended to eliminate
them if their effects are damaging enough. Others increase fitness (the 'good')
and are fixed by selection unless they are quickly lost by chance. Many are
neutral and have little or no effect on fitness (the 'indifferent'). Fixation
of any mutant leaves a trace in the DNA. Interpreting the combined traces
uncovered by modern DNA sequencing technology is one of the challenging tasks
at the cutting edge of population genetics.

Mutations have a wide impact throughout
biology and medicine and they often provide a route to identifying individual
genes and their mode of action. Population genetic analyses are crucial for understanding
the long-term dynamics of mutations. Rates of evolutionary change in traits
depend on rates of mutation and their fates. Sex is beneficial as a way of
recombining mutants. Adaptation of species to new environments, speciation, and
continuing improvement of plants and animals for food, all require mutation. However,
populations can also be damaged by too many mutations, especially if
environmental mutagens increase mutation rates. Thus many questions in modern
biology will benefit from a better understanding of mutations.

Such topics inform the background for the
scientific questions addressed by evolution@home. The state of the art on these
and related questions is now summarised in the latest themed print issue of the
Philosophical Transactions of the Royal Society of London B on 'The population
genetics of mutations: good, bad and indifferent'.

The issue is dedicated to Brian
Charlesworth's 65th birthday on 29 April 2010 to honour him for his many pioneering
studies in population genetics and evolutionary biology. Many of these continue
to inspire core ideas investigated by evolution@home simulations.

Brian Charlesworth, who teaches evolution
at the University of Edinburgh and heads the Institute of Evolutionary Biology LINK
there, has just published the new textbook “Elements of Evolutionary Genetics”
co-authored with his collaborator and wife Deborah Charlesworth. This book highlights
much of the basics needed for understanding the long-term consequences of
DNA-changes and other questions in evolution.

The papers in the latest themed print issue
of the oldest running scientific journal of the world cover a broad range of
studies around the population genetics of mutations, and contributors include
international leaders in the field. The preface and the introduction
are freely available at